Fundamental questions

How does the brain damage occur? Can we select at risk patients? What therapies do we have? How do they work? What is the side effect? What is the risk –benefit picture?

CBF & CPP

CBF-50ml/100g/min -750ml/min – 15-20% CO

20-25 ml/100g/min – cerebral impairment

15-20 ml/100g/min - isoelectric EEG

<10 ml/100g/min - irreversible damage

CPP = MAP – ICP : 80-100 –normal

<50 – slowing EEG ,cerebral impairment

25 - 40 – Flat EEG

<25 - irreversible damage

CBF- Auto regulation

CBF

MAP60 mmHg 160 mmHg

50

CBF &Variables

CBF depends on, PaCO2 (20-80mmHg)-1-2 ml/100g/min

/mmHg

T- 5-7%change/ 1 change

PaO2 <50 mmHg CBF

0

Cerebral protection

Cerebral protection -Strategies

Optimize CPP Decrease CMR Block the mediators of cell injury

- at ischemic cascade

- at reperfusion cascade

Protective techniques

Brain Shrinkage Hyperventilation Optimize CPP Appropriate BP

Hypothermia Decrease CMR Burst suppression

Pharmacological protectors -Block the mediators of cell injury

Brain shrinkage

T regulationo

Mild hypothermia

Moderate hypothermia

Profound hypothermia

Na-K pump failure

Na+

Ca+

Glutamate

Phosholipases

FFA

PL

ISCHEMIC CASCADE

TAXLTPG

OFR

Arachidonic acid

FFA

PL

REPERFUSION CASCADE

Endothelial damage&Platelet,WBC plugs

Pharmacological intervention

CMR Reduction Barbiturates: Decreases CMR

Decreases Ca+

Decreases OFR

Na+ channel blockade

Decreases Glucose entry

Decreases refractory ICP

Inverse steal blood flow

Pharmacological intervention

CMR Reduction Propofol, Etomidate Morphine, Fentanil, Sufentanil,

Remifentanil Diazepam, Midazolam Ketamine, Dexmedetomidine Halothane, Enflurane, Isoflurane,

Sevoflurane, Desflurane

Pharmacological intervention

Neuronal injury protectorsA} pre synaptic level- SNX III –Ca+ blocker

B} post synaptic level1.Na+ blocker- All volatile anaesthetic agents -Barbiturates -Lamotrigine - Riluzole -Lubeluzole2. Ca+ blocker -Nimodipine -Nicardipine

3.NMDA antagonists: Competitive blocker-Selfotel Non Competitive blocker-Dizoclypine -Dexromethorphan -ketamine

Pharmacological intervention

4.Glycine site analogues-felbamate, Licostinel

5.NO synthase inhibitors –lifarizine, 7nitroindazole

6.Mg+-Ca+ blockade, NMDA antagonist

7.steroids-anti inflammatory action, ?neuronal protection

-MPS, Tirilazad

8.OFR scavengers- Vit-E, PBN{phenyl derbuyl nitrone},

Tirilazad,Mannitol

9.Cytokinin inhibition-TNF Receptor I, TNF alfa mab

10. Anti adhesion molecule Ab